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United States Patent |
5,739,329
|
Sugiyama
|
April 14, 1998
|
Process for producing hexahydropyridazine and
hexahydropyridazine-1,2-dicarboxy derivative
Abstract
The present invention provides a process for producing a
hexahydropyridazine-1,2-dicarboxy derivative represented by the general
formula:
##STR1##
wherein R.sup.1 and R.sup.2 represent each independently an alkyl group,
by reacting a hydrazinedicarboxy derivative represented by the general
formula:
R.sup.1 OOC--NH--NH--COOR.sup.2 (1)
wherein R.sup.1 and R.sup.2 have the same meaning as mentioned above, with
a dihalogenobutane represented by the general formula:
X.sup.1 --CH.sub. CH.sub.2 CH.sub.2 CH.sub.2 --X.sup.2 (2)
wherein X.sup.1 and X.sup.2 represent each independently a halogen atom, in
the presence of an alkali metal hydroxide, characterized in that the above
reaction is effected in an aprotic polar solvent, and a process for
producing a hexahydropyridazine, characterized by decarboxylating the thus
obtained hexahydropyridazine-1,2-dicarboxy derivative (3) without
isolation in the presence of an alkali metal hydroxide and a
hydrogen-denoting compound.
Inventors:
|
Sugiyama; Tatsuo (Shizuoka-ken, JP)
|
Assignee:
|
Ihara Chemical Industry Co., Ltd. (Tokyo, JP)
|
Appl. No.:
|
530185 |
Filed:
|
October 5, 1995 |
PCT Filed:
|
February 10, 1995
|
PCT NO:
|
PCT/JP95/00184
|
371 Date:
|
October 5, 1995
|
102(e) Date:
|
October 5, 1995
|
PCT PUB.NO.:
|
WO95/21828 |
PCT PUB. Date:
|
August 17, 1995 |
Foreign Application Priority Data
| Feb 10, 1994[JP] | 6-037914 |
| Feb 10, 1994[JP] | 6-037915 |
Current U.S. Class: |
544/224; 544/235 |
Intern'l Class: |
C07D 237/04 |
Field of Search: |
544/224,235
|
References Cited
U.S. Patent Documents
2841584 | Jul., 1958 | Hunter | 544/224.
|
5310738 | May., 1994 | Nakayama | 544/224.
|
Foreign Patent Documents |
40785 | Apr., 1978 | JP.
| |
92-12136 | Jul., 1992 | WO | 544/224.
|
Other References
Abstract for JP 4-244067 (Sep. 1, 1992), Nakayama.
English translation of JP 40785 (Apr. 1978).
|
Primary Examiner: Bernhardt; Emily
Attorney, Agent or Firm: Oblon, Spivak, McClelland, Maier & Neustadt, P.C.
Claims
I claim:
1. A process for producing hexahydropyridazine, comprising reacting a
hydrazinedicarboxy compound represented by the formula:
R.sup.1 OOC--NH--NH--COOR.sup.2 ( 1)
wherein R.sup.1 and R.sup.2 represent each independently an alkyl group,
with a dihalogenobutane represented by the formula:
X.sup.1 --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 --X.sup.2 ( 2)
wherein X.sup.1 and X.sup.2 represent each independently a halogen atom, in
the presence of alkali metal hydroxide in an aprotic polar solvent to
obtain a hexahydropyridazine-1,2-dicarboxy compound represented by the
formula:
##STR4##
wherein R.sup.1 and R.sup.2 have the same meaning as defined above, and
decarboxylating this hexahydropyridazine-1,2-dicarboxy compound without
isolation in the presence of an alkali metal hydroxide and a
hydrogen-donating compound selected from the group consisting of water and
C.sub.1 -C.sub.6 alcohols.
2. The process according to claim 1, wherein in the compound of formula (1)
R.sup.1 and R.sup.2 are ethyl.
Description
TECHNICAL FIELD
The present invention relates to a process for producing a
hexahydropyridazine which is useful as an intermediate for benzothiazine
type agricultural chemicals (herbicide), and to a process for producing a
hexahydropyridazine-1,2-dicarboxy derivative which is useful as an
intermediate for producing this hexahydropyridazine.
BACKGROUND ART
The production of hexahydropyridazine has heretofore been carried out by
isolating a hexahydropyridazine-1,2-dicarboxy derivative and then
decarboxylating the same; however, no process for producing
hexahydropyridazine by decarboxylating the
hexahydropyridazine-1,2-dicarboxy derivative without isolation has been
known.
As a process for producing the above hexahydropyridazine-1,2-dicarboxy
derivative, the present inventors have already proposed a process by which
a hydrazinedicarboxy derivative represented by the general formula:
ROC--NH--NH--COR
wherein R represents an alkoxy group or an aryl group, is reacted with a
1,4-dihalogenobutane in the presence of a base selected from alkali metal
carbonates and hydroxides (see Japanese Patent Application Kokai No.
4-244,067).
However, this process has been unable to obtain the objective compound in a
sufficient yield in the case where an alkali metal hydroxide is used as
the base for a compound having the above formula for hydrazinedicarboxy
derivative in which R represents an alkoxy group.
An object of the present invention is to provide a process for producing
hexahydropyridazine simply and cheaply on an industrial scale.
Another object of the present invention is to provide a process for
producing a hexahydropyridazine-1,2-dicarboxy derivative which process has
solved the above-mentioned problems of prior art.
The present inventor has made extensive research for the purpose of
providing a process for producing a hexahydropyridazine-1,2-dicarboxy
derivative by which the above-mentioned problems of prior art have been
solved, and has, as a result, found that when in a process for producing a
hexahydropyridazine-1,2-dicarboxy derivative by reacting a
hydrazinedicarboxy derivative with a dihalogenobutane in the presence of
an alkali metal hydroxide, said reaction is conducted in an aprotic polar
solvent, the problems of prior art can be solved, and further found that
the hexahydropyridazine is obtained by such a simple procedure that the
thus obtained hexahydropyridazine-1,2-dicarboxy derivative is
decarboxylated without isolation using an alkali metal hydroxide. Based on
this findings, he has completed the present invention directed to a
process for producing hexahydropyridazine simply and cheaply on an
industrial scale.
DISCLOSURE OF THE INVENTION
That is to say, the first process of the present invention provides a
process for producing a hexahydropyridazine-1,2-dicarboxy derivative
represented by the general formula:
##STR2##
wherein R.sup.1 and R.sup.2 represent each independently an alkyl group,
by reacting a hydrazinedicarboxy derivative represented by the general
formula:
R.sup.1 OOC--NH--NH--COOR.sup.2 ( 1)
wherein R.sup.1 and R.sup.2 have the same meaning as above, with a
dihalogenobutane represented by the general formula:
X.sup.1 --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 --X.sup.2 ( 2)
wherein X.sup.1 and X.sup.2 represent each independently a halogen atom, in
the presence of an alkali metal hydroxide, characterized in that above
reaction is effected in an aprotic polar solvent.
The second process of the present invention provides a process for
producing hexahydropyridazine, characterized by reacting a
hydrazinedicarboxy derivative represented by the general formula:
R.sup.1 OOC--NH--NH--COOR.sup.2 ( 1)
wherein R.sup.1 and R.sup.2 represent each independently an alkyl group,
with a dihalogenobutane represented by the general formula:
X.sup.1 --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 --X.sup.2 ( 2)
wherein X.sup.1 and X.sup.2 represent each independently a halogen atom, in
the presence of an alkali metal hydroxide in an aprotic polar solvent to
obtain a hexahydropyridazine-1,2-dicarboxy derivative represented by the
general formula:
##STR3##
wherein R.sup.1 and R.sup.2 have the same meaning as above, and
decarboxylating this hexahydropyridazine-1,2-dicarboxy derivative without
isolation in the presence of an alkali metal hydroxide and a
hydrogen-donating compound.
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is explained in detail below.
In the present invention, first of all, according to the first process of
the present invention, the hydrazinedicarboxy derivative (1) is reacted
with the dihalogenobutane (2) in the presence of an alkali metal hydroxide
in an aprotic polar solvent to obtain a hexahydropyridazine-1,2-dicarboxy
derivative (3).
The hydrazinedicarboxy derivative (1) used as a starting material in the
first process of the present invention may be a compound of the above
formula in which R.sup.1 and R.sup.2 are each independently an alkyl
group, specifically, for example, an alkyl group having 1 to 8 carbon
atoms and a straight chain, branched chain or alicyclic structure, more
specifically such an alkyl group as a methyl group, an ethyl group, a
propyl group, an isopropyl group, a butyl group, a pentyl group, a hexyl
group, a cyclohexyl group, a heptyl group, an octyl group or the like. As
such compounds, specifically, for example, dimethyl
hydrazinedicarboxylate, diethyl hydrazinedicarboxylate, dibutyl
hydrazinedicarboxylate and the like can be mentioned as examples. However,
hydrazinedicarboxy derivatives (1) having substituents corresponding to
the structure of the objective hexahydropyridazine-1,2-dicarboxy
derivative (3) may be appropriately selected. Incidentally, compounds in
which R.sup.1 and R.sup.2 are the same substituent, are easily available
as the starting material.
The dihalogenobutane (2) used as a starting material in the first process
of the present invention may be a compound of the formula wherein X.sup.1
and X.sup.2 are each independently a halogen atom, specifically a
chlorine, a bromine, a fluorine or an iodine atom. In particular,
compounds of the formula in which they are chlorine atoms or bromine atoms
are easily available as the starting material and hence suitable. As such
compounds, 1,4-dichlorobutane, 1,4-dibromobutane, 1-bromo-4-chlorobutane
and the like can be mentioned as examples. Incidentally, this
dihalogenobutane (2) may, if desired, be used in admixture of two or more.
Moreover, as the alkali metal hydroxide used in the first process of the
present invention, those which are usually so called may be used and, for
example, sodium hydroxide and potassium hydroxide can be mentioned as
examples.
In the reaction in the first process of the present invention, as the mole
ratio of the hydrazinedicarboxy derivative (1), the dihalogenobutane (2)
and the alkali metal hydroxide used, a range of 1:(1-10):(1-20),
preferably 1:(1-2):(2-4) can be mentioned as an example.
In the first process of the present invention, an aprotic polar solvent is
used as the reaction solvent. As this aprotic polar solvent, those which
are usually called as aprotic polar solvents may be used, and
specifically, there can be mentioned, for example, amide type aprotic
polar solvents, representatives of which are N,N-dimethylformamide (DMF),
N,N-dimethylacetamide (DMAc), N,N-diethylacetamide (DEAc) and the like;
sulfur atom-containing aprotic polar solvents, representatives of which
are tetrahydrothiophene-1,1-dioxide (sulfolane), N,N-dimethyl sulfoxide
(DMSO) and the like; and others such as 1,3-dimethylimidazolidinone (DMI),
N,N-dimethyl propyleneurea (DMPU) and the like. These aprotic polar
solvents may be used, if necessary, in admixture of two or more. The
amount of the aprotic polar solvent used may be at least such an amount
that stirring is possible; however, usually an amount of 500 to 2,000 ml
per mole of the hydrazinedicarboxy derivative (1) is suitable.
The reaction in the first process of the present invention is effected in a
temperature range of from 10.degree. C. to 80.degree. C., preferably from
40.degree. C. to 70.degree. C., usually under atmospheric pressure, and
the reaction time is usually 30 minutes to 24 hours, preferably 1 to 5
hours. This reaction may be effected in the co-existence of a compound
capable of functioning as a phase transfer catalyst such as a quaternary
phosphonium salt, a quaternary ammonium salt, a crown ether, a
polyethylene glycol or the like.
Incidentally, the hydrazinedicarboxy derivative (1) used as the starting
material in the first process of the present invention can be easily
obtained by the method stated in Organic Synthesis Coll., Vol. III, 375.
In the present invention, according to the second process of the present
invention, the hexahydropyridazine-1,2-dicarboxy derivative (3) obtained
by reacting the hydrazinedicarboxy derivative (1), the dihalogenobutane
(2) and an alkali metal hydroxide as mentioned above in the presence of an
aprotic polar solvent is subsequently decarboxylated without isolation in
the presence of an alkali metal hydroxide and a hydrogen-donating compound
to produce hexahydropyridazine.
The alkali metal hydroxide used in the second process of the present
invention maybe the same as used in the reaction of the first process of
the present invention and specifically sodium hydroxide and potassium
hydroxide can be mentioned as examples. The alkali metal hydroxide used
here may be different from those used in the reaction for producing the
above hexahydropyridazine-1,2-dicarboxy derivative (3).
As the hydrogen-donating compound used in the second process of the present
invention, there can be mentioned, for example, compounds having a
hydroxyl group, more specifically, water; alcohols having 1 to 6 carbon
atoms and a straight chain, branched chain or ring structure such as
methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol,
n-pentanol, i-pentanol, n-hexanol, cyclohexanol and the like; etc. In
general, water is preferably used because it is easily available and can
easily be handled.
The amounts of the alkali metal hydroxide and hydrogen-donating compound
used in the second process of the present invention may be such that the
mole ratio of the hydrazinedicarboxy derivative (1) used in the prior
reaction: the alkali metal hydroxide: the hydrogen-donating compound is in
a range of 1:(2-20):(2-20), preferably 1:(4-8):(2-8).
In the second process of the present invention, the reaction mixture
obtained in the reaction for producing the
hexahydropyridazine-1,2-dicarboxy derivative (3) is used, so that usually,
it is not particularly necessary to add a solvent. However, if desired,
there may be added an aprotic polar solvent, specifically an amide type
aprotic polar solvent, representatives of which are N,N-dimethylformamide
(DMF), N,N-dimethylacetamide (DMAc), N, N-diethylacetamide (DEAc) and the
like; a sulfur atom-containing aprotic polar solvent, representatives of
which are tetrahydrothiophene-1,1-dioxide (sulfolane), N,N-dimethyl
sulfoxide (DMSO) and the like; or others such as
1,3-dimethylimidazolidinone (DMI), N,N-dimethylpropyleneurea (DMPU) and
the like. When an aprotic polar solvent is added, the aprotic polar
solvent to be added may be the same as or different from that used in the
reaction for the production of the above hexahydropyridazine-1,2-dicarboxy
derivative (3). The amount of the solvent added may be at least such an
amount that the reaction system can be stirred; however, it is suitable to
adjust the total solvent amount to fall in the range of from 500 ml to
2,000 ml per mole of the hydrazinedicarboxy derivative (1) used in the
reaction for producing the hexahydropyridazine-1,2-dicarboxy derivative
(3).
The reaction in the second process of the present invention is carried out
in a temperature range of from 80.degree. C. to 160.degree. C., preferably
from 90.degree. C. to 120.degree. C., usually under atmospheric pressure;
however, the reaction maybe effected under pressure. The reaction time is
1 to 24 hours, preferably 2 to 8 hours.
Incidentally, when the isolated hexahydropyridazine-1,2-dicarboxy
derivative (3) was used and subjected to decarboxylation in the presence
of an alkali metal hydroxide and a hydrogen-donating compound in an
aprotic polar solvent, the production of the hexahydropyridazine which was
the objective compound of the present process was not confirmed.
The present invention is specifically explained below referring to Examples
and Comparative Examples.
EXAMPLE 1
Production (1) of diethyl hexahydropyridazine-1,2-dicarboxylate
Into a 500-ml, four-necked flask equipped with a reflux condenser, a
stirrer and a thermometer were charged 35.2 g (0.2 mole) of diethyl
hydrazinedicarboxylate, 25.9 g (0.204 mole) of 1,4-dichlorobutane, 200 ml
of 1,3-dimethylimidazolidinone and 22.4 g (0.4 mole) of potassium
hydroxide, gradually warmed up to 50.degree.-60.degree. C. and aged for 3
hours. After completion of the reaction, the reaction mixture was cooled
and filtered to remove the solid matters, after which the solvent was
removed by distillation under reduced pressure. The residue obtained was
distilled under reduced pressure (110.degree. C./1 mmHg) to obtain 33.0 g
of diethyl hexahydropyridazine-1,2-dicarboxylate. The yield was 72%.
EXAMPLE 2
Production (2) of diethyl hexahydropyridazine-1,2-dicarboxylate
The same procedure as in Example 1 was carried out, except that 200 ml of
N,N-dimethylformamide was substituted for the 200 ml of
1,3-dimethylimidazolidinone. As a result, 27.6 g of diethyl
hexahydropyridazine-1,2-dicarboxylate was obtained. The yield was 60%.
EXAMPLE 3
Production (1) of hexahydropyridazine
Into a four-necked flask equipped with a reflux condenser, a stirrer and a
thermometer were charged 176 g (1.0 mole) of diethyl
hydrazinedicarboxylate, 129.5 g (1.02 moles) of 1,4-dichlorobutane, 1
liter of 1,3-dimethylimidazolidinone and 112.4 g (2.0 moles) of potassium
hydroxide, gradually warmed up to 50.degree. C.-60.degree. C., and then
subjected to reaction for 3 hours in this temperature range. After the
reaction, the reaction mixture was cooled and filtered. To the filtrate
obtained were added 224.4 g (4.0 moles) of potassium hydroxide and 72 g
(4.0 moles) of water and the temperature was elevated to 100.degree.
C.-110.degree. C., after which the mixture was aged in the same
temperature range for 4 hours, cooled and filtered to remove the inorganic
salt. The filtrate was rectified to obtain 53 g of hexahydropyridazine
having a boiling point of 38.degree. C./8 mmHg. The yield was 61.6%.
EXAMPLE 4
Production (2) of hexahydropyridazine
The same procedure as in Example 3 was carried out, except that 1 liter of
N,N-dimethylpropyleneurea was substituted for the 1 litter of
1,3-dimethylimidazolidinone. As a result, 44.5 g of hexahydropyridazine
was obtained. The yield was 51.7%.
EXAMPLE 5
Production (3) of hexahydropyridazine
Into a four-necked flask equipped with a reflux condenser, a stirrer and a
thermometer were charged 176 g (1.0 mole) of diethyl
hydrazinedicarboxylate, 129.5 g (1.02 moles) of 1,4-dichlorobutane, 2
liters of N,N-dimethylformamide and 112.4 g (2.0 moles) of potassium
hydroxide, gradually warmed up to 50.degree.-60.degree. C. and subjected
to reaction for 3 hours in this temperature range. After the reaction, the
reaction mixture was cooled and filtered, after which 336.6 g (6.0 moles)
of potassium hydroxide and 108 g (6.0 moles) of water were added to the
filtrate obtained. The temperature was elevated to 100.degree.-110.degree.
C. and stirring was continued for 4 hours in this temperature range, after
which the mixture was cooled and filtered to remove the inorganic salt.
The filtrate was rectified to obtain 52 g (yield: 60.5% ) of
hexahydropyridazine having a boiling point of 38.degree. C./8 mmHg.
EXAMPLE 6
Production (4) of hexahydropyridazine
Into a four-necked flask equipped with a reflux condenser, a stirrer and a
thermometer were charged 176 g (1.0 mole) of diethyl
hydrazinedicarboxylate, 129.5 g (1.02 moles) of 1,4-dichlorobutane, 1
litter of tetrahydrothiophene-1,1-dioxide (sulfolane) and 112.4 g (2.0
moles) of potassium hydroxide, gradually warmed up to
50.degree.-60.degree. C., and subjected to reaction for 3 hours in this
temperature range. After the reaction, the reaction mixture was cooled and
filtered, and to the filtrate obtained were added 224.4 g (4.0 moles) and
72 g (4.0 moles) of water. The temperature was elevated to
100.degree.-110.degree. C. and stirring was continued for 4 hours in this
temperature range, after which the mixture was cooled and filtered to
remove the inorganic salt. The filtrate was rectified to obtain 50 g
(yield: 58.1%) of hexahydropyridazine having a boiling point of 38.degree.
C./8 mmHg.
COMPARATIVE EXAMPLE 1
Decarboxylation of isolated diethylhexahydropyridazine-1,2-dicarboxylate
Into a 100-ml, four-necked flask equipped with a reflux condenser, a
stirrer and a thermometer were charged 50 ml of
1,3-dimethylimidazolidinone, 5.75 g (0.025 mole) of diethyl
hexahydropyridazine-1,2-dicarboxylate ›produced according to the method of
(Example 1), isolated and purified!, 5.61 g (0.1 mole) of potassium
hydroxide and 0.9 g (0.05 mole) of water and stirred for 1.5 hours in a
temperature range of 100.degree.-110.degree. C. At this stage, the
reaction mixture was analyzed. The objective hexahydropyridazine was not
detected. In this analysis, the peak of the diethyl
hexahydropyridazine-1,2-dicarboxylate added as a starting material has
disappeared.
INDUSTRIAL APPLICABILITY
According to the first process of the present invention, unlike the
conventional process, even when such a compound that R.sup.1 and R.sup.2
in the formula for hydrazinedicarboxy derivative (1) are alkyl groups and
a dihalogenobutane (2) are used as the starting materials and an alkali
metal hydroxide is used as a base, it has become possible to produce a
hexahydropyridazine-1,2-dicarboxy derivative (3) simply and cheaply on a
commercial scale.
Also, according to the second process of the present invention,
hexahydropyridazine can be produced by such a simple procedure that the
hexahydropyridazine-1,2-dicarboxy derivative (3) produced from the
hydrazinedicarboxy derivative (1) and the dihalogenobutane (2) is
subjected, without isolation, to decarboxylation. Accordingly, in view of
simplicity of operation, not only is it suitable for the production of
hexahydropyridazine on a industrial scale, but also is it important as a
process for producing a useful intermediate for a benzothiazine type
herbicide (see Japanese Patent Application Kokai No. 63-264,489).
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